Effect of dexamethasone or HWA-138 in combination with antibiotics in experimental Haemophilus influenzae type b infection

Abstract

Modulation of the host's inflammatory response in bacterial meningitis may be beneficial. In this study, the effects of dexamethasone and HWA-138, an analog of pentoxifylline, on CSF cultures and cochlear inflammation in an infant rat model of Haemophilus influenzae type b were studied. Five-day-old infant rats were inoculated once intraperitoneally with 1 x 104 to 10 x i04 CFU of H. influenzae type b (strain 1406). Twenty-four hours later, infant rats were treated intraperitoneally with one dose of ampicillin (0.1 mg/g of body weight), cefotaxime (0.05 mg/g), or cefuroxime (0.05 mg/g) alone or in combination with one dose of dexamethasone (0.00015 mg/g) or HWA-138 (0.005 mg/g). Twenty-four hours after treatment with cefuroxime plus dexamethasone, animals had a significantly (P c 0.04) greater incidence of bacteremia and meningitis (eight of nine animals) than that in animals of the other treatment groups. Overall, dexamethasone was associated with less inflammation (P < 0.04) of the cochlear nerve compared with that from antibiotic treatment alone. In this model, when suboptimal antimicrobial therapy is administered, anti-inflammatory agents may be beneficial with respect to reducing cochlear inflammation. However, dexamethasone and cefuroxime lead to a higher rate of positive blood and cerebral spinal fluid cultures than cefuroxime alone.

Retracted: Haemophilus influenzae responds to glucocorticoids used in asthma therapy by modulation of biofilm formation and antibiotic resistance

“…In a mouse model, beclomethasone increased the persistence of H. influenzae and reduced the efficacy of azithromycin in clearing the infection. These latter findings are consistent with previous observations using an infant mouse model of bacterial meningitis, where dexamethasone was shown to enhance the persistence of H. influenzae in blood and cerebral spinal fluid from mice undergoing treatment with the oral antibiotic cefuroxime (Rodriguez et al , 1991 ). The effects of glucocorticosteroid on the behavior of H. influenzae in mice may also be mediated by influences on the host as well as by direct effects on the bacterium.…”

Effect of betamethasone and diclofenac sodium on serum and tissue concentration of amoxicillin: in vivo study in rats

“…The phagocytic cells are a major component of host resistance against bacteria and any drug that impairs their function is likely to increase susceptibility to infection 21 . However, the modulation of the inflammatory response of infectious diseases could be beneficial since the sequelae relate, in part, to this reaction 23 .…”

Adjunctive Therapy for Bacterial Meningitis

“…31 Furthermore, Rodriguez and colleagues showed that dexamethasone did not affect CSF penetration of ampicillin, cefotaxime, or cefuroxime in infant rat model of H. influenzae meningitis. 32 In an experimental model of pneumococcal meningitis, concomitant administration of dexamethasone has been demonstrated to reduce entry of vancomycin into CSF and to reduce the rate of bactericidal killing. Neither rifampicin nor ceftriaxone was affected by…”